J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from Journal of , Neurosurgery, and Psychiatry, 1976, 39, 105-113

Trigeminal neuropathy with nasal ulceration: report of two cases and one necropsy

J. D. SPILLANE AND H. URICH From the Department of Neurology, University Hospital of Wales, Cardiff, and the Institute ofPathology, The London Hospital, London

SYN OP SI s Two cases are reported of progressive trigeminal neuropathy with nasal ulceration. One patient developed signs of involvement 15 years after the onset of trigeminal symptoms and died after a total course of 21 years. Necropsy revealed an unusual trigeminospinal system degeneration with deposition of amyloid-like substances in the affected structures. The other patient is alive eight years after the onset of symptoms, the only indication of a outside the trigeminal being a patch of numbness in one leg. guest. Protected by copyright. In a previous paper on isolated trigeminal were absent and the sensations of touch, neuropathy (Spillane and Wells, 1959) one of us , and temperature were impaired in the first and described a patient with total bilateral trigeminal second divisions on both sides, loss being absolute loss accompanied by progressive ulceration of for all modalities on the left side. There were slighter changes in both third divisions. Deep pressure and her nose (case 15). We now wish to report the vibration sense were normal. Taste was absent in the subsequent evolution of her condition and post- anterior two-thirds of the tongue. She could not mortem findings which we believe to be unique. appreciate the temperature of food on the left side We also wish to record another patient who dis- played similar symptoms and signs, at least in the early stages of her disease.

CASE 1 CLINICAL HISTORY A widow, aged 59 years, was first seen in 1950. Her illness began in 1949 with redness and pain of both eyes. She attended an ophthalmic clinic where a diagnosis of bilateral keratocon- junctivitis (Sjogren's disease) was made. A few http://jnnp.bmj.com/ months later a red, tender, and painful sore appeared at the edge of her left nostril. Biopsy in 1950 showed a hyperkeratotic lesion with superficial but no evidence of neoplasm. The sore increased in size and the outer margin of the nostril was pro- gressively eroded. In January 1951 both sides of her forehead became numb; six months later her left upper lip was numb. Thereafter, numbness spread on September 29, 2021 by rapidly over the whole of the left side of her face and in August 1951 over the right side of her face. Her mouth and tongue became dry. In October 1951 there was bilateral keratoconjunctivitis with small irregular pupils and bilateral corneal opacities. Her ( i 1t-1 left nostril was ulcerated (Fig. la and b). The corneal FIG. 1 Case 1. Two years after onset; erosioni of (Accepted 19 August 1975.) left ala nasi, bilateralptosis, anrd neuropathic keratitis. 105 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

106 J. D. Spillane and H. Urich of her mouth. There was no involveement of the no contraction of masticatory muscles could be motor root of either trigeminal nervie. There was palpated. There was almost total bilateral trigeminal no symptom or sign of involvement elsewhere in the anaesthesia. Hearing remained normal, speech and investigations iwere entirely intelligible. By the mid-'60s she was becoming un- negative. No evidence of syphilis, , steady on her feet and she often stumbled and fell. systemic , or scleroderma emerged. Sphincter functions were not affected. She com- Over the years her condition stead]ily worsened. plained that her legs were cold and she often By 1957 her nose was totally eroded (Fig. 2a and b), wrapped them in a shawl and retired to bed. The she was profoundly anaemic and siie lost much lower limbs were very thin but arterial pulsations at weight. Eyesight was grossly impaired because of the ankles were normal. Knee and ankle jerks were corneal opacities, she chewed and swtallowed with gradually reduced and subsequently lost. Extensor plantar reflexes were first detected in 1965 and remained until her death five years later. No sensory abnormality was found in her lower limbs until 1966 when posture and vibration could not be appreci- ated in her feet. Subsequently, vibration could not be appreciated below the knees. Superficial sensation was impaired only distally and never profoundly. In her upper limbs, superficial sensation did not seem to be impaired, although grips were weak and hands clumsy. There was postural and vibration loss in the t hands; the arm reflexes were never lost. She remainedguest. Protected by copyright. able to feed herself with difficulty until her terminal illness. She was alert and orientated until the end. / Thus, this strange neurological illness began in the trigeminal sensory system and some 15 years later §S involved the spinal cord. There were no clues to its nature.

...... NECROPSY FINDINGS (West Cardiff Area Laboratory :-, x P.M. 213/70) There were no significant abnormali- ties outside the nervous system. In particular there was no evidence of generalized , multiple FIG. 2 Case 1. Six years later; total destruction of myeloma, systemic lupus erythematosus, or any nose, bilateral trigeminal anaesthesia. other multisystemic disease. EXAMINATION OF NERVOUS SYSTEM (L.H. P.M. 4/A/71) The macroscopic appearances of the brain difficulty, and had no sense of taste. Nevertheless, were unremarkable. Transverse sections through the alert and spinal cord showed symmetrical greyish discolora- she remained uncomplaining; repeated http://jnnp.bmj.com/ neurological examinations were otherwise negative. tion in the posterior parts of the lateral columns and There was still no sign of involvement of the motor in the posterior columns, particularly the fasciculus roots of the trigeminal but the sensory loss gracilis. had progressed. She could scarcely detect the presence of food in her mouth. Sensory loss was MICROSCOPIC APPEARANCES The were con- more or less complete in both first and second fined to the trigeminal nerve and its pathways, and divisions of the trigeminal nerves; it was impaired to the long tracts of the spinal cord. sensation was in both third divisions. Deep impaired. on September 29, 2021 by There was bilateral ptosis, small pupils, and loss of SENSORY ROOT OF TRIGEMINAL NERVE The entire secretions from lacrimal and salivary glands. She root from its entry into the pons to the proximity of retained a very feeble sense of smell. the Gasserian ganglion was severely affected. The From 1958 onwards, until her death in 1970 from glial part of the root was devoid of and bronchopneumonia at the age of 78 years, she re- sheaths and showed astrocytic proliferation with fused hospital admission and neurological examina- fibrillary gliosis. Distal to the glio-Schwannian tions had to be made in her home. In the 1960s she junction, the root was infiltrated by an abnormal became very thin, her jaw movements were weak and substance, consisting of two components, A and B, J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

Trigeminal neuropathy with nasal ulceration: report of two cases and one necropsy 107

TABLE STAINING REACTIONS OF INFILTRATING SUBSTANCES

Method Substance Control (sporadic amyloid neuropathy) A B Congo red+ polarized light Weakly positive birefringent, Negative Strongly to weakly positive dichroic, polarization colour birefringent, dichroic, green polarization colour green Sirius red+ polarized light Positive birefringent, dichroic, Negative Positive birefringent, dichroic polarization colour green polarization colour green Wolman's toluidine blue + polarized Purplish blue birefringent, Blue Purplish blue birefringent, light dichroic, polarization colour dichroic, polarization colour red red Crystal violet Gamma metachromasia (red) Beta metachromasia Gamma metachromasia (red) (purple) Lendrum's sodium sulphate-alcian Green Khaki Green blue-van Gieson Thioflavin T Greenish fluorescence Greenish fluorescence Greenish fluorescence Luxol-fast blue-cresyl violet Light blue Dark blue Light blue guest. Protected by copyright.

'S -- ->f>...... ' .Ej . Kap1'-. -t .,jU S . . S .

FIG. 3 Case 1. Trigeminal root; infiltration ofglio-Schwannian junction by amyloid-like material. Lighter component represents substance A, darker substance B. Crystal violet, x 90. http://jnnp.bmj.com/ on September 29, 2021 by with different staining reactions (Table). Substance beading in places (Fig. 4). The infiltration stopped A was abundant at the junction, gradually giving short of the entry of the sensory root into the way to infiltration with substance B (Fig. 3). trigeminal ganglion where some deposits of substance Throughout its length, the root was devoid of axons A again became apparent. Throughout the length of and myelin sheaths, the individual fibres being the root the walls of blood vessels were infiltrated infiltrated with substance B. This formed solid or with substance B. tubular strands varying in thickness, with a some- what irregular outline and a tendency to coarse GASSERIAN GANGLION The neurones of the trig- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

108 J. D. Spillane and H. Urich

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FIG. 4 Case 1. Trigeminal root: infiltration along the FIG. 5 Case 1. Trigeminal root: tangled whorls of course of nerve fibres and in walls of blood vessels. large calibre nerve fibres, probably derivedfrom motor Thioflavin T (Mercury vapour lamp, exciter filter root. Glees-Marsland silver impregnation, x 120. Schott UGJ, barrier filter Schott -50), x 200.

meninal ganglion were remarkably well preserved in traumatic of the nerve roots (Fig. 5). and only a few cells showed evidence of degeneration Their origin could not be traced with certainty, but in the form of loss of nuclei and poor cytoplasmic their position and calibre of axons suggested that http://jnnp.bmj.com/ staining. Proliferation of capsule cells was seen in a they were derived from the motor root. few places, but there were no nodules of Nageotte or other evidence of neuronal loss. The nerve fibres CENTRAL TRIGEMINAL PATHWAYS The intrapontine within the ganglion showed some degenerative course of the sensory trigeminal fibres showed total changes in the form of irregular beading, or club- loss of axons and myelin sheaths. No obvious shaped, spherical, or ovoid retraction bulbs. A few lesions were seen in the motor, principal sensory, and argyrophilic baskets were present around neuronal mesencephalic nuclei of the 5th nerve. On the other cell bodies. The peripheral branches of the trigeminal hand, the spinal trigeminal tract showed severe on September 29, 2021 by nerves were not available for examination, but fibre degeneration and its nucleus marked, but not total, bundles emerging from the ganglion contained loss of neurones. In addition, the blood vessels within abundant well myelinated axons. the tract and the nucleus were thickened and their walls infiltrated with an abnormal homogeneous MOTOR ROOT OF TRIGEMINAL NERVE Medial to the material showing the staining reactions of substance entry of the sensory root into the pons there were B (Fig. 6). This infiltration, of variable thickness, skeins of well-myelinated large axons forming appeared to be predominantly adventitial and did irregularly convoluted whorls, resembling those seen not encroach upon the lumen of the vessels. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

Trigeminal neuropathy with nasal ulceration: report of two cases and one necropsy 109

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FIG. 6 Case 1. Nucleus of spinal tract of trigeminal nerve: total loss of myelinated fibres in tract and infiltration of walls of blood vessels. Luxolfast blue-cresyl violet, 'V x 60.

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I FIG. 7 Case 1. Cervical cord: degeneration of crossed pyramidal tracts and of fasciculus gracilis; infiltration of blood vessels in lateral columns only. Luxol fast blue-cresyl violet, x 10. http://jnnp.bmj.com/ SPINAL CORD Throughout the spinal cord there was vascular changes extended into the medullary almost total loss of myelinated fibres in the crossed pyramids, but not above that level. pyramidal tracts, the uncrossed tracts being un- The posterior columns showed rarefaction, but affected (Fig. 7). On tracing the lesions into the not total loss, of fibres in the lumbar segments. This medullary pyramids, the fibre loss became less loss became more severe at higher levels, and in the conspicuous and at pontine level no abnormality cervical segments was almost total in the fasciculus could be detected in the corticospinal tracts. gracilis, the fasciculus cuneatus being well preserved.

Throughout the degenerate lateral columns the By contrast with the pyramidal tracts, abnormal on September 29, 2021 by blood vessels showed conspicuous changes similar vessels were almost completely absent in the to those described above. The thickening and degenerated parts of the posterior columns. infiltration appeared to be mainly adventitial, but some vessels showed medial thickening with sub- DORSAL ROOT GANGLIA A few random posterior intimal infiltration and possibly some narrowing of root ganglia available for examination showed no the lumen. The infiltrating material was almost significant lesions. exclusively substance B, but tiny fragments of substance A were found in some vessels. These MENINGEAL VESSELS A few vessels in the ventral cleft J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

110 J. D. Spillane and H. Urich of the spinal cord showed infiltration with substance Neuroradiological studies (pneumoencephalography B. The vessels over the surface of the cord showed no and vertebral angiography) were normal. Blood and abnormality. A few circumferential vessels of the spinal fluid were normal. Serum proteins and electro- brain stem showed traces of substance B in their phoresis were normal and the ESR was 15 mm/lh. walls. The blood vessels over and in the cerebral In December 1968 she began to notice a numbness hemispheres showed no abnormality. of her right cheek, by which time the left-sided numbness had spread to involve the forehead and CASE 2 eye. The corneal was absent on the left and there was a left-sided Homer syndrome (Fig. 8a). A married woman, aged 38 years, with one child was On that side, the sensory loss was now dense and she first seen in 1968. No significant previous illnesses developed a neuropathic keratitis which required were recorded. Onset of left-sided trigeminal tarsorraphy. On the right side, during the following occurred in September 1967. There were no year, the numbness spread over the whole face. In trigger phenomena; inter-paroxysmal facial aching June 1969 further investigations were normal except caused insomnia. was ineffective. for a raised sedimentation rate (48 mm/lh). By early The skin on the affected side of the face was drier 1970 she had lost 9 kg (20 lb) in weight since the than on the right. In January 1968 the facial beginning of her illness. She found chewing and began to subside but they were replaced by numbness swallowing difficult and would lose the food in her and paraesthesiae. There was no other neurological mouth. A right tarsorraphy was necessary. When her involvement. By February 1968 there was impair- eyes were closed she could scarcely appreciate ment of taste on the left side; tongue, gums, and passive movements of the tip of the nose or of herguest. Protected by copyright. cheek on the left side all felt numb. Examination upper lip. Taste was absent except for a fleeting confirmed impairment of touch, pain, and tempera- sensation during the act of swallowing. There was ture in the distribution of the second and third now probable weakness of the masticatory muscles. divisions of the left trigeminal nerve. There was no ESR was 56 mm/lh; DAT 1 in 256. Prednisone 5 mg motor trigeminal impairment. Corneal reflexes were thrice daily was begun in February 1970. There was retained. Investigations revealed no evidence of no change during 1970 but in January 1971 early syphilis, sarcoidosis, systemic lupus, or scleroderma. erosion of the left ala nasi was detected (Fig. 8b), and http://jnnp.bmj.com/ on September 29, 2021 by

FIG. 8 Case 2. (a) Fifteen months after onset; left Horner syndrome, left trigeminal sensory loss, absent left corneal reflex, early neuropathic keratitis, early sensory loss on right cheek. (b) Two years later; early erosion ofleft ala nasi. Bilateral trigeminal anaesthesia with bilateral neuropathic keratitis. (c) One year later; erosion ofnasal septum and collapse ofnose. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

Trigeminal neuropathy with nasal ulceration: report of two cases and one necropsy III during the course of that year the whole of the nasal either case. A spinal cord lesion developed in the septum disintegrated and her nose collapsed (Fig. first case after some 15 years. In the second case, 8c). No bacilli were discovered in her nose the only other sign to appear, after eight years, and nasal biopsy showed no evidence of granuloma. is a patch of numbness on the left leg. No During the years 1972 and 1973 there was no new evidence of systemic disease was found in either development. Her general condition was poor, her died 21 after the weight remained at about 50 kg (110 lb) and she case. The first patient years was depressed. The soft tissues of the nose shrank beginning of her illness. The second patient but did not disappear as in case 1. She was provided remains at work as a domestic help. with a nasal prosthesis and she continued her work In the literature of trigeminal neuropathy as a domestic help. Sedimentation rates were recorded there are several references to its occurrence in during these years at 34 and 52 mm/I h respectively. association with connective tissue disease Serum proteins and electrophoresis remained nor- (Beighton et al., 1968; Kaltreider and Talal, mal; negative antinuclear factor; positive rheumatoid 1969; Gumpel, 1970a, b; Ashworth and Tait, screening test, DAT 1 in 4. 1971 ; Lundberg and Werner, 1972; Whaley et al., Early in 1974, while in her bath, she discovered a 1973). In the majority ofthese cases the presenta- patch of numbness on the outer side of the left leg below the knee. It has persisted unchanged until the tion of illness was not with the trigeminal lesion; present (June 1975) and measured about 5 cm by the latter usually appeared during the course of 3.8 cm (2 in. by 12 in.) and appears to be in the area the systemic disorder. Lundberg and Werner supplied by the musculocutaneous nerve. There is no suggested that the neuropathy is caused by guest. Protected by copyright. alteration of the skin and no thickening of nerves. vascular lesions in the medulla because of the Electrodiagnostic tests were normal. The sensory sparing of the corneal reflexes and the occasional loss involves all modalities but it is not complete. bilateral nature of the disorder of the trigeminal Her general health has improved, she has put on sensory system. Barraquer-Bordas et al. (1973) 5.4 kg in weight and is less depressed. She is taking question this interpretation of the signs in prednisone 5 mg daily. Her nervous system is other- bilateral cases. The relationship of unilateral wise normal. In recent months there have been several episodes of postural vertigo which have trigeminal sensory neuropathy to Bell's palsy subsided; menstruation has been irregular. There appears to be a tenuous one (Seward, 1962; has been no sign of returning trigeminal sensibility. Ch'ien and Halsey, 1970; Eggleston and There is virtual bilateral total superficial anaes- Haskell, 1972). thesia; vibration cannot be appreciated on the malar Shafar and Copp (1970) have described a case or mandibular prominences; passive movements of in which unilateral trigeminal sensory neuro- the tip of the nose and upper lips remain only feebly pathy was the only manifestation of widespread appreciated. for a period of 10 years. So in this case, also, we have a presentation of a It is obvious that nerve conduction studies may lesion in both trigenimal sensory systems, erosion of when the only the nose, but so far the only indication of a lesion reveal involvement of limb nerves elsewhere in the nervous system consists of a patch clinical feature remains numbness of the face. http://jnnp.bmj.com/ of numbness on one leg. None of these associations was found in our first patient on postmortem examination. The lesions consisted of degeneration of the trige- DISCUSSION minal root and its central pathways, and of the Both cases presented with trigeminal sensory pyramidal tracts and posterior columns in the loss which, in the first case, was bilateral from spinal cord. This was associated with deposition the outset, and in the second case became

of an amyloid-like substance. The degeneration on September 29, 2021 by bilateral after 15 months. Trophic erosion of the of the affected tracts was not accompanied by nose took place in each case. The trigeminal significant lesions in their cells of origin, suggest- sensory loss was not dissociated; all superficial ing a 'dying-back' mechanism. The association modalities were involved from the outset; deep of trigeminal lesions with long tract degenera- pressure and vibration became affected later. tions is unusual and we are not aware of a Taste was lost. Signs of involvement of the similar combination reported either in genetic or trigeminal motor system also eventually oc- sporadic system degenerations. curred. No other cranial nerve was involved in The infiltrating substance was confined to J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

112 J. D. Spillane and H. Urich connective tissue structures and involved the logical position of this localized Gasserian walls of the blood vessels in the affected tracts amyloidosis remains uncertain. It is also of to in the central nervous system. In the trigeminal interest that hyaline bodies, mainly related root root, it was apparently deposited on the endo- blood vessels, were found in the dorsal surrounding the degenerated fibres as ganglia in cases of hereditary sensory radicular neurium and well as on blood vessels, the infiltration stopping neuropathy studied by Denny-Brown (1951) abruptly at the glio-Schwannian junction. The by van Bogaert (1953), but not in other similar substance consisted of two components, differing cases. The material on Denny-Brown's case in their staining properties, one sparse and stained with Congo red. found predominantly at the glio-Schwannian In the central nervous system amyloid deposi- junction (substance A), the other abundant and tion is common in the 'congophilic ' widely distributed (substance B). According to in the cerebral cortex of old people, sometimes the criteria laid down by Wolman (1971) for associated with senile dementia of the Alzheimer identification of amyloid-like substances, type (Corsellis and Brierley, 1954). In his ex- material showing all the specific staining tensive studies on senile amyloidosis of the reactions is 'amyloid', that showing only some cardiovascular system, Schwartz (1969) em- of them is 'pseudoamyloid'. By these criteria, phasized this involvement of cortical vessels, any our substance A represents true amyloid, but did not mention similar changes in substance B pseudoamyloid. Regrettably, no other part of the central nervous system. guest. Protected by copyright. material containing substance A was available The strict association of the vascular for electron microscopy. Its fibrillary structure amyloidosis or pseudoamyloidosis with tract can only be inferred from its optical properties degenerations in our case suggests a causal such as birefringence and dichroism. The ultra- relationship between the two processes. It could structure of substance B was homogeneous and be argued that the vascular lesions were the would therefore be designated by some authori- primary event, and the tract degenerations ties as 'hyaline', a term reserved by Wolman for represented a summation effect of multiple material showing none of the staining reactions ischaemic lesions leading to Wallerian degenera- of amyloid. The relationship between amyloid tion. This problem has its counterpart in and pseudoamyloid, or amyloid and hyaline, peripheral amyloid neuropathy, which, in remains obscure. It is, however, of interest that Kernohan and Woltman's (1942) view, repre- Coimbra and Andrade (1971a) observed deposi- sented an ischaemic neuropathy due to oblitera- tion of hyaline as well as fibrillary amyloid in tion of the . Doubts on this early cases of the Portuguese variant of familial interpretation were cast when Dyck and Lambert amyloid neuropathy and suggested that the (1969) demonstrated a selective loss of un- hyaline material might be a precursor of true myelinated axons and when Coimbra and that fibre degenera- amyloid. Andrade (1971b) suggested http://jnnp.bmj.com/ The distribution of amyloid-like substances in tion preceded the deposition of amyloid. Simi- our case was unusual and has no counterpart in larly, Schwartz's view that amyloidosis was the any known type of amyloidosis. It bears no cause of senile dementia was refuted by Wis- resemblance to any form of amyloid neuropathy, niewski and Terry (1973). In our case, it would familial or sporadic (reviewed by Henson and appear unlikely that a primary vascular disease Urich, 1970 and by Urich, 1976). Two unusual should be confined to well-defined tracts. There a mention, that of Daly et al. was no evidence that the patency of the vessels cases deserve brief on September 29, 2021 by (1957) and of Borghi and Tagliabue (1961). In was significantly impaired and there were no both these cases, amyloid deposits were found in focal areas of ischaemic necrosis. We therefore Gasserian ganglia removed surgically for the prefer to interpret the findings as a primary treatment of . At the time of system degeneration and the deposition of operation these patients showed no evidence of amyloid-like substances as an epiphenomenon. systemic amyloidosis or peripheral neuropathy, It remains to be explained why these vascular and their trigeminal symptoms were unilateral. changes are not seen more frequently in system In the absence of follow-up studies the noso- degenerations. It is well known that amyloid J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.2.105 on 1 February 1976. Downloaded from

Trigeminal neuropathy with nasal ulceration: report of two cases and one necropsy 113 deposition may be due to generalized distur- peripheral nerve in five cases. 1. Interstitial changes. Brain, 94, 199-206. bances, such as excess of circulating light chain Coimbra, A., and Andrade, C. (1971b). Familial amyloid immunoglobulins, or to strictly local causes, : an electron microscope study of the as in types of tumours. peripheral nerve in five cases. 2. Nerve fibre changes. such observed certain Brain, 94, 207-212. In addition, it may be suggested that in some Corsellis, J. A. N., and Brierley, J. B. (1954). An unusual cases the interplay of local and general factors type of presenile dementia (atypical Alzheimer's disease may be responsible both for the deposition and with amyloid vascular change). Brain, 77, 571-587. Daly, D. D., Love, J. G., and Dockerty, M. B. (1957). for the localisation of amyloid. To quote Amyloid tumour of Gasserian ganglion. Journal of Neuro- Schwartz (1969) '. .. amyloid is precipitated surgery, 14, 347-352. when a morbid factor circulating in the blood, Denny-Brown, D. (1951). Hereditary sensory radicular neuropathy. Journal of Neurology, Neurosurgery, and lymph, or cerebrospinal liquor, joins a compound Psychiatry, 14, 237-252. located in diseased structural elements of tissues Dyck, P. J., and Lambert, E. H. (1969). Dissociated sensation and cells'. Perhaps the lesions in our case in amyloidosis. Archives of Neurology (Chic.), 20, 490-507. Eggleston, D. J., and Haskell, R. (1972). Idiopathic trigeminal represent an example of senile amyloidosis sensory neuropathy. Practitioner, 208, 649-655. localized in degenerating nervous tissue. Gumpel, J. M. (1970a). Isolated trigeminal neuropathy. There is at present no indication that the Lancet, 1, 310. condition of our second patient is due to a Gumpel, J. M. (1970b). Trigeminal sensory neuropathy in connective tissue disease. New EnglandJournal ofMedicine, similar combination or distribution of lesions. 282, 514.

So, while trigeminal neuropathy with progressive Henson, R. A., and Urich, H. (1970). Metabolic neuropathies. guest. Protected by copyright. nasal ulceration forms a distinct clinical syn- In Handbook of Clinical Neurology, vol. 8, pp. 1-28. Edited by P. J. Vinken and G. W. Bruyn. North Holland: Amster- drome, it would be premature to suggest that it dam. constitutes a nosological entity. Kaltreider, H. B., and Talal, N. (1969). The neuropathy of Sjogren's syndrome; trigeminal nerve involvement. Annals We are indebted to Dr N. G. Sanerkin for his necropsy of Internal Medicine, 70, 751-762. findings and for referring the material for further Kernohan, J. W., and Woltman, H. W. (1942). Amyloid examination. . Archives ofNeurology and Psychiatry, 47, 132-140. Lundberg, P. O., and Werner, I. (1972). Trigeminal sensory REFERENCES neuropathy in systemic lupus erythematosus. Acta Neuro- Scandinavica, 48, 330-340. B. W. Trigeminal neuro- logica Ashworth, B., and Tait, G. (1971). Schwartz, P. (1969). Cardiovascular amyloidosis in the aged. pathy in connective tissue disease. Neurology (Minneap.), Geriatrics, 24/8, 81-97. 21, 609-614. A Barraquer-Bordas, L., Torrent, R., Codina, M., and Solans, Seward, M. H. E. (1962). Anaesthesia of the lower lip. T. (1973). Neuropathie sensitive du trijumeau, pure, problem in differential diagnosis. British Dental Journal, bilaterale, avec troubles trophiques oculaires. Revue 113, 423-426. Neurologique, 129, 222-226. Shafar, J., and Copp, E. P. (1970). Isolated trigeminal Beighton, P. H., Gumpel, J. M., and Cornes, N. G. M. (1968). neuropathy. Lancet, 1, 242-243. Prodromal trigeminal sensory neuropathy in progressive Spillane, J. D., and Wells, C. E. C. (1959). Isolated trigeminal systemic sclerosis. Annals of Rheumatic Diseases, 27, neuropathy: a report of 16 cases. Brain, 82, 391-416. 367-369. Urich, H. (1976). Diseases of peripheral nerves. In Green- Bogaert, L. van (1953). Etude histopathologique d'une field's , 3rd edn. Edited by W. Blackwood observation d' arthropathie mutilante symetrique familiale. and J. A. N. Corsellis. Arnold: London. (In press.) http://jnnp.bmj.com/ Sa non-appartenance a la syringomyelie. Ses rapports avec Whaley, K., Webb, J., McAvoy, B. A., Hughes, G. R. V., la neuropathie radiculaire sensorielle hereditaire (Hicks et Lee, P., MacSween, R. N. M., and Buchanan, W. W. (1973). Denny-Brown). Acta Neurologica et Psychiatrica Belgica, Sjogren's syndrome; clinical associations and immuno- 53, 37-54. logical phenomena. Quiarterly Journal of Medicine, 42, Borghi, G., and Tagliabue, G. (1961). Primary amyloidosis 513-548. in the Gasserian ganglion. Acta Neuirologica et Psychiatrica Wiiniewski, H. M., and Terry, R. D. (1973). Morphology of Scandinavica, 37, 105-110. the aging brain, human and animal. Progress in Brain Ch'ien, L. T., and Halsey, J. H. (1970). Trigeminal sensory Research, 40, 167-186. neuropathy and Bell's palsy. New England Journal of Wolman, M. (1971). Amyloid, its nature and molecular Medicine, 282, 224-225. structure. Comparison of a new toluidine blue polarized on September 29, 2021 by Coimbra, A., and Andrade, C. (1971a). Familial amyloid light method with traditional procedures. Laboratory polyneuropathy: an electron miscroscope study of the Investigation, 25, 104-1 10.